The present invention relates generally to methods and devices aimed at reducing a harmful effect of ischemia and reperfusion injury of an organ with the overall purpose of reducing the final infarct size and loss of function by the organ. More particularly, the invention describes methods and designs for blood pressure cuffs configured to deliver remote ischemic preconditioning and monitor blood pressure of the patient.
Coronary heart disease is a leading cause of mortality and morbidity in the Western world and is projected to be a leading cause of death worldwide by year 2020. Acute myocardial infarction (AMI) is the main cause of such mortality. Although major advances in treatments over the last four decades have translated into a considerable decline in mortality rates after AMI, heart failure became a common complication for survivors, with the estimated post-infarct incidences between 10% and 40%. Post-infarct heart failure is a debilitating disease associated with high mortality, with a median survival of only 4 years. In the United States, the American Heart Association estimates the total number of patients living with heart failure today to be 5.3 million with 660 thousand new patients diagnosed every year. Direct and indirect treatments for these patients cost approximately $35 billion a year representing the single highest disease burden of all healthcare costs.
In patients with acute myocardial infarction, rapid restoration of blood flow (reperfusion) either by primary percutaneous coronary intervention or thrombolysis is the most effective treatment for myocardial salvage. However, it has now been shown that reperfusion itself has the potential to induce additional lethal injury that is not present at the end of the ischemic period. This injury is called an ischemia/reperfusion injury or simply a reperfusion injury. Reperfusion injury is a contributing factor in many other diseases, most notably including acute stroke, acute trauma, acute compartment syndrome, etc. Management of planned ischemia events during CABG, AAA and other types of surgery may also benefit from reducing the consequences of reperfusion injury.
A new treatment to induce ischemic tolerance and reduce the harmful effects of reperfusion injury is known as ischemic preconditioning. Other terms used in the literature to describe this intervention include “ischemic postconditioning”, “ischemic perconditioning”, and “ischemic conditioning”. For the purposes of this description, all procedures describing a series of sub-lethal interruptions of blood flow are described using the general term “ischemic preconditioning” whether it is done prior to, during, or after the ischemia as well as prior to, during, or after reperfusion. Remote ischemic preconditioning describes one version of this treatment, which includes applying a series of brief sub-lethal episodes of ischemia and reperfusion to an organ other than the target ischemic organ (such ischemic organ may be a heart or a brain). This treatment triggers activation of Reperfusion Injury Salvage Kinases (RISK) pathways as well as strong anti-apoptosis and anti-inflammatory effects. Applying a series of brief ischemic stimulae to a distant organ before, during, or after restoration of normal perfusion of the target ischemic organ is shown to activate protection from ischemia for the whole body and therefore reduces ischemia-reperfusion damage of the target organ. Over the years, a number of distant organs have been shown to provide cardioprotection in the setting of remote ischemic preconditioning including skeletal muscles on upper and lower extremities. Applying a preconditioning procedure externally to an upper or lower limb is especially attractive as it is non-invasive, easy to implement, and safe. Blood flow to the limb during the procedure is typically occluded for 3-5 min by a manually- or automatically-inflated blood pressure cuff or a tourniquet cuff. A deflation interval of 3-5 min then follows and this cycle is repeated 3-4 times. An overview of this procedure and the mechanisms of action are described for example by Kharbanda R K, Nielsen T T, and Redington A N. “Translation of remote ischemic preconditioning into clinical practice”, Lancet 374:1557-1565, 2009, incorporated herein by reference in its entirety.
Although the following description discusses applying remote ischemic preconditioning to a subject or patient (both terms are used to mean the same for the purposes of this specification) suffering from acute myocardial infarction to reduce infarct size, it is not limited to this clinical application alone. As mentioned above, this treatment can be applied to acute stroke and trauma patients including those suffering from traumatic brain injury, as well as to patients during, prior or after various interventions or surgeries when blood flow to an organ is temporarily interrupted or a release of embolic particles is likely. They can also be applied in organ and tissue transplant surgeries as well as in other clinical applications.
U.S. Pat. No. 7,717,855 to Caldarone et al. incorporated herein by reference in its entirety discloses one example of an automatic device configured to deliver remote ischemic preconditioning by periodic inflation and deflation of a cuff placed about a limb of a patient. Blood flow through the limb is interrupted by inflating the cuff to a set pressure above the systolic blood pressure of the patient. One sited example of such set pressure is 200 mmHg. This approach has a limitation in that inflating the cuff to such high pressure for extended periods of time may cause pain and discomfort to the patient. For most of the patients, there is no need to inflate the cuff to 200 mmHg to achieve total limb occlusion. On the other hand, in a small portion of the patients with high or rapidly changing blood pressure (with systolic blood pressure exceeding 200 mmHg), the set inflation pressure approach may not be sufficient to occlude the limb adequately.
Patients suffering from an acute myocardial infarction or stroke require close monitoring of their vital signs and blood pressure in particular. Deterioration of blood pressure may cause profound ischemia and multi-organ failure. Emergency medicine guidelines recommend checking patient's blood pressure every 3-5 minutes especially after administering vasodilators such as nitroglycerin. It is envisioned that upon a first contact with a medical practitioner and confirmation of diagnosis, a heart attack patient would need initiation of ischemic preconditioning and vital signs monitoring almost at the same time. Occupying one arm with a preconditioning cuff will require using another arm for a traditional blood pressure monitoring cuff. This two-arm arrangement is not only cumbersome but may also cause interruption of intra-venous injections during the periods of blood pressure measurements when the cuff is inflated and occludes blood flow to the arm.
It is therefore desirable to frequently monitor blood pressure for signs of hemodynamic deterioration and conduct ischemic preconditioning on the same arm, leaving the second arm for uninterrupted intra-venous injections. The need also exists for a device capable of delivering preconditioning at the lowest possible cuff pressure so as to reduce patient's discomfort and pain.